REFERENCES
2. Chiurazzi P, Pirozzi F. Advances in understanding - genetic basis of intellectual disability. F1000Res 2016;5:F1000. Faculty Rev-599
3. Khan MA, Khan S, Windpassinger C, Badar M, Nawaz Z, et al. The molecular genetics of autosomal recessive nonsyndromic intellectual disability: a mutational continuum and future recommendations. Ann Hum Genet 2016;80:342-68.
5. Hu H, Kahrizi K, Musante L, Fattahi Z, Herwig R, et al. Genetics of intellectual disability in consanguineous families. Mol Psychiatry 2019;24:1027-39.
6. Salcedo-Arellano MJ, Dufour B, McLennan Y, Martinez-Cerdeno V, Hagerman R. Fragile X syndrome and associated disorders: clinical aspects and pathology. Neurobiol Dis 2020;136:104740.
7. Glasson EJ, Buckley N, Chen W, Leonard H, Epstein A, et al. Systematic review and meta-analysis: mental health in children with neurogenetic disorders associated with intellectual disability. J Am Acad Child Adolesc Psychiatry 2020:S0890-8567(20)30008-3.
8. Antonarakis SE, Skotko BG, Rafii MS, Strydom A, Pape SE, et al. Down syndrome. Nat Rev Dis Primers 2020;6:9.
9. Musante L, Puttmann L, Kahrizi K, Garshasbi M, Hu H, et al. Mutations of the aminoacyl-tRNA-synthetases SARS and WARS2 are implicated in the etiology of autosomal recessive intellectual disability. Hum Mutat 2017;38:621-36.
10. Abedini SS, Kahrizi K, de Pouplana LR, Najmabadi H. tRNA methyltransferase defects and intellectual disability. Arch Iran Med 2018;21:478-85.
12. Chan PP, Lowe TM. GtRNAdb 2.0: an expanded database of transfer RNA genes identified in complete and draft genomes. Nucleic Acids Res 2015;44:D184-9.
13. Torres AG. Enjoy the silence: nearly half of human trna genes are silent. Bioinform Biol Insights 2019;13:1177932219868454.
14. Matthaei JH, Jones OW, Martin RG, Nirenberg MW. Characteristics and composition of rna coding units. Proc Natl Acad Sci U S A 1962;48:666-77.
15. Nishikura K, De Robertis EM. RNA processing in microinjected Xenopus oocytes. Sequential addition of base modifications in the spliced transfer RNA. J Mol Biol 1981;145:405-20.
16. Jiang HQ, Motorin Y, Jin YX, Grosjean H. Pleiotropic effects of intron removal on base modification pattern of yeast tRNAPhe: an in vitro study. Nucleic Acids Res 1997;25:2694-701.
18. Ohira T, Suzuki T. Retrograde nuclear import of tRNA precursors is required for modified base biogenesis in yeast. Proc Natl Acad Sci U S A 2011;108:10502-7.
19. Agris PF, Eruysal ER, Narendran A, Vare VYP, Vangaveti S, et al. Celebrating wobble decoding: half a century and still much is new. RNA Biol 2018;15:537-53.
20. Vare VY, Eruysal ER, Narendran A, Sarachan KL, Agris PF. Chemical and conformational diversity of modified nucleosides affects trna structure and function. Biomolecules 2017;7:29.
21. Grosjean H, Westhof E. An integrated, structure- and energy-based view of the genetic code. Nucleic Acids Res 2016;44:8020-40.
22. Johansson MJ, Esberg A, Huang B, Bjork GR, Bystrom AS. Eukaryotic wobble uridine modifications promote a functionally redundant decoding system. Mol Cell Biol 2008;28:3301-12.
23. Rezgui VA, Tyagi K, Ranjan N, Konevega AL, Mittelstaet J, et al. tRNA tKUUU, tQUUG, and tEUUC wobble position modifications fine-tune protein translation by promoting ribosome A-site binding. Proc Natl Acad Sci U S A 2013;110:12289-94.
24. Vendeix FA, Murphy FVt, Cantara WA, Leszczynska G, Gustilo EM, et al. Human tRNA(Lys3)(UUU) is pre-structured by natural modifications for cognate and wobble codon binding through keto-enol tautomerism. J Mol Biol 2012;416:467-85.
25. Ranjan N, Rodnina MV. Thio-modification of tRNA at the wobble position as regulator of the kinetics of decoding and translocation on the ribosome. J Am Chem Soc 2017;139:5857-64.
26. Roovers M, Oudjama Y, Kaminska KH, Purta E, Caillet J, et al. Sequence-structure-function analysis of the bifunctional enzyme MnmC that catalyses the last two steps in the biosynthesis of hypermodified nucleoside mnm5s2U in tRNA. Proteins 2008;71:2076-85.
27. Nedialkova DD, Leidel SA. Optimization of codon translation rates via tRNA modifications maintains proteome integrity. Cell 2015;161:1606-18.
28. Tukenmez H, Xu H, Esberg A, Bystrom AS. The role of wobble uridine modifications in +1 translational frameshifting in eukaryotes. Nucleic Acids Res 2015;43:9489-99.
29. Klassen R, Bruch A., Schaffrath R. Independent suppression of ribosomal +1 frameshifts by different tRNA anticodon loop modifications. RNA Biol 2017;14:1252-9.
30. Woese CR, Olsen GJ, Ibba M, Soll D. Aminoacyl-tRNA synthetases, the genetic code, and the evolutionary process. Microbiol Mol Biol Rev 2000;64:202-36.
31. Torres AG, Batlle E, Ribas de Pouplana L. Role of tRNA modifications in human diseases. Trends Mol Med 2014;20:306-14.
32. Pechmann S, Willmund F, Frydman J. The ribosome as a hub for protein quality control. Mol Cell 2013;49:411-21.
33. Antonellis A, Green ED. The role of aminoacyl-tRNA synthetases in genetic diseases. Annu Rev Genomics Hum Genet 2008;9:87-107.
34. Meyer-Schuman R, Antonellis A. Emerging mechanisms of aminoacyl-tRNA synthetase mutations in recessive and dominant human disease. Hum Mol Genet 2017;26:R114-27.
35. Sissler M, Gonzalez-Serrano LE, Westhof E. Recent advances in mitochondrial aminoacyl-tRNA synthetases and disease. Trends Mol Med 2017;23:693-708.
36. Fuchs SA, Schene IF, Kok G, Jansen JM, Nikkels PGJ, et al. Aminoacyl-tRNA synthetase deficiencies in search of common themes. Genet Med 2019;21:319-30.
37. Freude K, Hoffmann K, Jensen LR, Delatycki MB, des Portes V, et al. Mutations in the FTSJ1 gene coding for a novel S-adenosylmethionine-binding protein cause nonsyndromic X-linked mental retardation. Am J Hum Genet 2004;75:305-9.
38. Hamel BC, Smits AP, van den Helm B, Smeets DF, Knoers NV, et al. Four families (MRX43, MRX44, MRX45, MRX52) with nonspecific X-linked mental retardation: clinical and psychometric data and results of linkage analysis. Am J Med Genet 1999;85:290-304.
39. Hirata A, Okada K, Yoshii K, Shiraishi H, Saijo S, et al. Structure of tRNA methyltransferase complex of Trm7 and Trm734 reveals a novel binding interface for tRNA recognition. Nucleic Acids Res 2019;47:10942-55.
40. Jensen LR, Garrett L, Holter SM, Rathkolb B, Racz I, et al. A mouse model for intellectual disability caused by mutations in the X-linked 2’Omethyltransferase Ftsj1 gene. Biochim Biophys Acta Mol Basis Dis 2019;1865:2083-93.
41. Ramser J, Winnepenninckx B, Lenski C, Errijgers V, Platzer M, et al. A splice site mutation in the methyltransferase gene FTSJ1 in Xp11.23 is associated with non-syndromic mental retardation in a large Belgian family (MRX9). J Med Genet 2004;41:679-83.
42. Ropers HH, Hoeltzenbein M, Kalscheuer V, Yntema H, Hamel B, et al. Nonsyndromic X-linked mental retardation: where are the missing mutations? Trends Genet 2003;19:316-20.
43. Wang R, Lei T, Fu F, Li R, Jing X, et al. Application of chromosome microarray analysis in patients with unexplained developmental delay/intellectual disability in South China. Pediatr Neonatol 2019;60:35-42.
44. Willems P, Vits L, Buntinx I, Raeymaekers P, Van Broeckhoven C, et al. Localization of a gene responsible for nonspecific mental retardation (MRX9) to the pericentromeric region of the X chromosome. Genomics 1993;18:290-4.
45. Pintard L, Kressler D, Lapeyre B. Spb1p is a yeast nucleolar protein associated with Nop1p and Nop58p that is able to bind S-adenosyl-L-methionine in vitro. Mol Cell Biol 2000;20:1370-81.
46. Abbasi-Moheb L, Mertel S, Gonsior M, Nouri-Vahid L, Kahrizi K, et al. Mutations in NSUN2 cause autosomal-recessive intellectual disability. Am J Hum Genet 2012;90:847-55.
47. Brzezicha B, Schmidt M, Makalowska I, Jarmolowski A, Pienkowska J, et al. Identification of human tRNA:m5C methyltransferase catalysing intron-dependent m5C formation in the first position of the anticodon of the pre-tRNA Leu (CAA). Nucleic Acids Res 2006;34:6034-43.
48. Frye M, Watt FM. The RNA methyltransferase Misu (NSun2) mediates Myc-induced proliferation and is upregulated in tumors. Curr Biol 2006;16:971-81.
49. Khan MA, Rafiq MA, Noor A, Hussain S, Flores JV, et al. Mutation in NSUN2, which encodes an RNA methyltransferase, causes autosomal-recessive intellectual disability. Am J Hum Genet 2012;90:856-63.
50. Kuss AW, Garshasbi M, Kahrizi K, Tzschach A, Behjati F, et al. Autosomal recessive mental retardation: homozygosity mapping identifies 27 single linkage intervals, at least 14 novel loci and several mutation hotspots. Hum Genet 2011;129:141-8.
51. Martinez FJ, Lee JH, Lee JE, Blanco S, Nickerson E, et al. Whole exome sequencing identifies a splicing mutation in NSUN2 as a cause of a Dubowitz-like syndrome. J Med Genet 2012;49:380-5.
52. Najmabadi H, Motazacker MM, Garshasbi M, Kahrizi K, Tzschach A, et al. Homozygosity mapping in consanguineous families reveals extreme heterogeneity of non-syndromic autosomal recessive mental retardation and identifies 8 novel gene loci. Hum Genet 2007;121:43-8.
53. Sakita-Suto S, Kanda A, Suzuki F, Sato S, Takata T, et al. Aurora-B regulates RNA methyltransferase NSUN2. Mol Biol Cell 2007;18:1107-17.
54. Tuorto F, Liebers R, Musch T, Schaefer M, Hofmann S, et al. RNA cytosine methylation by Dnmt2 and NSun2 promotes tRNA stability and protein synthesis. Nat Struct Mol Biol 2012;19:900-5.
55. Blanco S, Dietmann S, Flores JV, Hussain S, Kutter C, et al. Aberrant methylation of tRNAs links cellular stress to neuro-developmental disorders. EMBO J 2014;33:2020-39.
56. Abdelrahman HA, Al-Shamsi AM, Ali BR, Al-Gazali L. A null variant in PUS3 confirms its involvement in intellectual disability and further delineates the associated neurodevelopmental disease. Clin Genet 2018;94:586-7.
57. Braun DA, Shril S, Sinha A, Schneider R, Tan W, et al. Mutations in WDR4 as a new cause of Galloway-Mowat syndrome. Am J Med Genet A 2018;176:2460-5.
58. Chen X, Gao Y, Yang L, Wu B, Dong X, et al. Speech and language delay in a patient with WDR4 mutations. Eur J Med Genet 2018;61:468-72.
59. Claudio JO, Liew CC, Ma J, Heng HH, Stewart AK, et al. Cloning and expression analysis of a novel WD repeat gene, WDR3, mapping to 1p12-p13. Genomics 1999;59:85-9.
60. Lin S, Liu Q, Lelyveld VS, Choe J, Szostak JW, et al. Mettl1/Wdr4-mediated m(7)G tRNA methylome is required for normal mRNA translation and embryonic stem cell self-renewal and differentiation. Mol Cell 2018;71:244-55.e5.
61. Michaud J, Kudoh J, Berry A, Bonne-Tamir B, Lalioti MD, et al. Isolation and characterization of a human chromosome 21q22.3 gene (WDR4) and its mouse homologue that code for a WD-repeat protein. Genomics 2000;68:71-9.
62. Shaheen R, Abdel-Salam GM, Guy MP, Alomar R, Abdel-Hamid MS, et al. Mutation in WDR4 impairs tRNA m(7)G46 methylation and causes a distinct form of microcephalic primordial dwarfism. Genome Biol 2015;16:210.
63. Trimouille A, Lasseaux E, Barat P, Deiller C, Drunat S, et al. Further delineation of the phenotype caused by biallelic variants in the WDR4 gene. Clin Genet 2017;93:374-7.
64. Blaesius K, Abbasi AA, Tahir TH, Tietze A, Picker-Minh S, et al. Mutations in the tRNA methyltransferase 1 gene TRMT1 cause congenital microcephaly, isolated inferior vermian hypoplasia and cystic leukomalacia in addition to intellectual disability. Am J Med Genet A 2018;176:2517-21.
65. Davarniya B, Hu H, Kahrizi K, Musante L, Fattahi Z, et al. The role of a novel TRMT1 gene mutation and rare GRM1 gene defect in intellectual disability in two azeri families. PLoS One 2015;10:e0129631.
66. Liu JM, Straby KB. The human tRNA(m(2)(2)G(26))dimethyltransferase: functional expression and characterization of a cloned hTRM1 gene. Nucleic Acids Res 2000;28:3445-51.
67. Najmabadi H, Hu H, Garshasbi M, Zemojtel T, Abedini SS, et al. Deep sequencing reveals 50 novel genes for recessive cognitive disorders. Nature 2011;478:57-63.
68. Xu F, Zhou Y, Bystrom AS, Johansson MJO. Identification of factors that promote biogenesis of tRNA(CGA)(Ser). RNA Biol 2018;15:1286-94.
69. Dewe JM, Fuller BL, Lentini JM, Kellner SM, Fu D. TRMT1-catalyzed tRNA modifications are required for redox homeostasis to ensure proper cellular proliferation and oxidative stress survival. Mol Cell Biol 2017;37:e00214-17.
70. Zhang K, Lentini JM, Prevost CT, Hashem MO, Alkuraya FS, et al. An intellectual disability-associated missense variant in TRMT1 impairs tRNA modification and reconstitution of enzymatic activity. Hum Mutat 2020;41:600-7.
71. Alazami AM, Hijazi H, Al-Dosari MS, Shaheen R, Hashem A, et al. Mutation in ADAT3, encoding adenosine deaminase acting on transfer RNA, causes intellectual disability and strabismus. J Med Genet 2013;50:425-30.
72. El-Hattab AW, Saleh MA, Hashem A, Al-Owain M, Asmari AA, et al. ADAT3-related intellectual disability: further delineation of the phenotype. Am J Med Genet A 2016;170A:1142-7.
73. Gerber AP, Keller W. An adenosine deaminase that generates inosine at the wobble position of tRNAs. Science 1999;286:1146-9.
74. Ramos J, Han L, Li Y, Hagelskamp F, Kellner SM, et al. Formation of tRNA wobble inosine in humans is disrupted by a millennia-old mutation causing intellectual disability. Mol Cell Biol 2019;39:e00203-19.
75. Salehi Chaleshtori AR, Miyake N, Ahmadvand M, Bashti O, Matsumoto N, et al. A novel 8-bp duplication in ADAT3 causes mild intellectual disability. Hum Genome Var 2018;5:7.
76. Sharkia R, Zalan A, Jabareen-Masri A, Zahalka H, Mahajnah M. A new case confirming and expanding the phenotype spectrum of ADAT3-related intellectual disability syndrome. Eur J Med Genet 2019;62:103549.
77. Thomas E, Lewis AM, Yang Y, Chanprasert S, Potocki L, et al. Novel missense variants in ADAT3 as a cause of syndromic intellectual disability. J Pediatr Genet 2019;8:244-51.
78. Fu Y, Dai Q, Zhang W, Ren J, Pan T, et al. The AlkB domain of mammalian ABH8 catalyzes hydroxylation of 5-methoxycarbonylmethyluridine at the wobble position of tRNA. Angew Chem Int Ed Engl 2010;49:8885-8.
79. Monies D, Vagbo CB, Al-Owain M, Alhomaidi S, Alkuraya FS. Recessive truncating mutations in ALKBH8 cause intellectual disability and severe impairment of wobble uridine modification. Am J Hum Genet 2019;104:1202-9.
80. Shimada K, Nakamura M, Anai S, De Velasco M, Tanaka M, et al. A novel human AlkB homologue, ALKBH8, contributes to human bladder cancer progression. Cancer Res 2009;69:3157-64.
81. Tsujikawa K, Koike K, Kitae K, Shinkawa A, Arima H, et al. Expression and sub-cellular localization of human ABH family molecules. J Cell Mol Med 2007;11:1105-16.
82. Arrondel C, Missoury S, Snoek R, Patat J, Menara G, et al. Defects in t(6)A tRNA modification due to GON7 and YRDC mutations lead to Galloway-Mowat syndrome. Nat Commun 2019;10:3967.
83. Braun DA, Rao J, Mollet G, Schapiro D, Daugeron MC, et al. Mutations in KEOPS-complex genes cause nephrotic syndrome with primary microcephaly. Nat Genet 2017;49:1529-38.
84. Edvardson S, Prunetti L, Arraf A, Haas D, Bacusmo JM, et al. tRNA N6-adenosine threonylcarbamoyltransferase defect due to KAE1/TCS3 (OSGEP) mutation manifest by neurodegeneration and renal tubulopathy. Eur J Hum Genet 2017;25:545-51.
85. Miyoshi A, Kito K, Aramoto T, Abe Y, Kobayashi N, et al. Identification of CGI-121, a novel PRPK (p53-related protein kinase)-binding protein. Biochem Biophys Res Commun 2003;303:399-405.
86. Gillis D, Krishnamohan A, Yaacov B, Shaag A, Jackman JE, et al. TRMT10A dysfunction is associated with abnormalities in glucose homeostasis, short stature and microcephaly. J Med Genet 2014;51:581-6.
87. Howell NW, Jora M, Jepson BF, Limbach PA, Jackman JE. Distinct substrate specificities of the human tRNA methyltransferases TRMT10A and TRMT10B. RNA 2019;25:1366-76.
88. Igoillo-Esteve M, Genin A, Lambert N, Desir J, Pirson I, et al. tRNA methyltransferase homolog gene TRMT10A mutation in young onset diabetes and primary microcephaly in humans. PLoS Genet 2013;9:e1003888.
89. Krishnamohan A, Jackman JE. Mechanistic features of the atypical tRNA m1G9 SPOUT methyltransferase, Trm10. Nucleic Acids Res 2017;45:9019-29.
90. Krishnamohan A, Jackman JE. A family divided: distinct structural and mechanistic features of the SpoU-TrmD (SPOUT) methyltransferase superfamily. Biochemistry 2019;58:336-45.
91. Yew TW, McCreight L, Colclough K, Ellard S, Pearson ER. tRNA methyltransferase homologue gene TRMT10A mutation in young adult-onset diabetes with intellectual disability, microcephaly and epilepsy. Diabet Med 2016;33:e21-5.
92. Zung A, Kori M, Burundukov E, Ben-Yosef T, Tatoor Y, et al. Homozygous deletion of TRMT10A as part of a contiguous gene deletion in a syndrome of failure to thrive, delayed puberty, intellectual disability and diabetes mellitus. Am J Med Genet A 2015;167A:3167-73.
93. Cohen JS, Srivastava S, Farwell KD, Lu HM, Zeng W, et al. ELP2 is a novel gene implicated in neurodevelopmental disabilities. Am J Med Genet A 2015;167:1391-5.
94. Dalwadi U, Yip CK. Structural insights into the function of Elongator. Cell Mol Life Sci 2018;75:1613-22.
95. Dauden MI, Kosinski J, Kolaj-Robin O, Desfosses A, Ori A, et al. Architecture of the yeast Elongator complex. EMBO Rep 2017;18:264-79.
96. Hawkes NA, Otero G, Winkler GS, Marshall N, Dahmus ME, et al. Purification and characterization of the human elongator complex. J Biol Chem 2002;277:3047-52.
97. Johansson MJO, Xu F, Byström AS. Elongator—a tRNA modifying complex that promotes efficient translational decoding. Biochim Biophys Acta Gene Regul Mech 2018;1861:401-8.
98. Karlsborn T, Tukenmez H, Mahmud AK, Xu F, Xu H, et al. Elongator, a conserved complex required for wobble uridine modifications in eukaryotes. RNA Biol 2014;11:1519-28.
99. Addis L, Ahn JW, Dobson R, Dixit A, Ogilvie CM, et al. Microdeletions of ELP4 are associated with language impairment, autism spectrum disorder, and mental retardation. Hum Mutat 2015;36:842-50.
100. Hu P, Meng L, Ma D, Qiao F, Wang Y, et al. A novel 11p13 microdeletion encompassing PAX6 in a Chinese Han family with aniridia, ptosis and mental retardation. Mol Cytogenet 2015;8:3.
101. Strug LJ, Clarke T, Chiang T, Chien M, Baskurt Z, et al. Centrotemporal sharp wave EEG trait in rolandic epilepsy maps to Elongator Protein Complex 4 (ELP4). Eur J Hum Genet 2009;17:1171-81.
102. Dewez M, Bauer F, Dieu M, Raes M, Vandenhaute J, et al. The conserved Wobble uridine tRNA thiolase Ctu1-Ctu2 is required to maintain genome integrity. Proc Natl Acad Sci U S A 2008;105:5459-64.
103. Rapino F, Delaunay S, Rambow F, Zhou Z, Tharun L, et al. Codon-specific translation reprogramming promotes resistance to targeted therapy. Nature 2018;558:605-9.
104. Schlieker CD, Van der Veen AG, Damon JR, Spooner E, Ploegh HL. A functional proteomics approach links the ubiquitin-related modifier Urm1 to a tRNA modification pathway. Proc Natl Acad Sci U S A 2008;105:18255-60.
105. Shaheen R, Al-Salam Z, El-Hattab AW, Alkuraya FS. The syndrome dysmorphic facies, renal agenesis, ambiguous genitalia, microcephaly, polydactyly and lissencephaly (DREAM-PL): report of two additional patients. Am J Med Genet A 2016;170:3222-6.
106. Shaheen R, Mark P, Prevost CT, AlKindi A, Alhag A, et al. Biallelic variants in CTU2 cause DREAM-PL syndrome and impair thiolation of tRNA wobble U34. Hum Mutat 2019;40:2108-20.
107. Shaheen R, Patel N, Shamseldin H, Alzahrani F, Al-Yamany R, et al. Accelerating matchmaking of novel dysmorphology syndromes through clinical and genomic characterization of a large cohort. Genet Med 2016;18:686-95.
108. Alfares A, Alfadhel M, Wani T, Alsahli S, Alluhaydan I, et al. A multicenter clinical exome study in unselected cohorts from a consanguineous population of Saudi Arabia demonstrated a high diagnostic yield. Mol Genet Metab 2017;121:91-5.
109. Chen J, Patton JR. Pseudouridine synthase 3 from mouse modifies the anticodon loop of tRNA. Biochemistry 2000;39:12723-30.
110. Shaheen R, Han L, Faqeih E, Ewida N, Alobeid E, et al. A homozygous truncating mutation in PUS3 expands the role of tRNA modification in normal cognition. Hum Genet 2016;135:707-13.
111. Shaheen R, Tasak M, Maddirevula S, Abdel-Salam GMH, Sayed ISM, et al. PUS7 mutations impair pseudouridylation in humans and cause intellectual disability and microcephaly. Hum Genet 2019;138:231-9.
112. Becker HF, Motorin Y, Planta RJ, Grosjean H. The yeast gene YNL292w encodes a pseudouridine synthase (Pus4) catalyzing the formation of psi55 in both mitochondrial and cytoplasmic tRNAs. Nucleic Acids Res 1997;25:4493-9.
113. Bykhovskaya Y, Casas K, Mengesha E, Inbal A, Fischel-Ghodsian N. Missense mutation in pseudouridine synthase 1 (PUS1) causes mitochondrial myopathy and sideroblastic anemia (MLASA). Am J Hum Genet 2004;74:1303-8.
114. Fernandez-Vizarra E, Berardinelli A, Valente L, Tiranti V, Zeviani M. Nonsense mutation in pseudouridylate synthase 1 (PUS1) in two brothers affected by myopathy, lactic acidosis and sideroblastic anaemia (MLASA). J Med Genet 2007;44:173-80.
115. Massenet S, Motorin Y, Lafontaine DL, Hurt EC, Grosjean H, et al. Pseudouridine mapping in the Saccharomyces cerevisiae spliceosomal U small nuclear RNAs (snRNAs) reveals that pseudouridine synthase pus1p exhibits a dual substrate specificity for U2 snRNA and tRNA. Mol Cell Biol 1999;19:2142-54.
116. Patton JR, Bykhovskaya Y, Mengesha E, Bertolotto C, Fischel-Ghodsian N. Mitochondrial myopathy and sideroblastic anemia (MLASA): missense mutation in the pseudouridine synthase 1 (PUS1) gene is associated with the loss of tRNA pseudouridylation. J Biol Chem 2005;280:19823-8.
117. Zeharia A, Fischel-Ghodsian N, Casas K, Bykhocskaya Y, Tamari H, et al. Mitochondrial myopathy, sideroblastic anemia, and lactic acidosis: an autosomal recessive syndrome in Persian Jews caused by a mutation in the PUS1 gene. J Child Neurol 2005;20:449-52.
118. Brouwer APM, Abou Jamra R, Kortel N, Soyris C, Polla DL, et al. Variants in PUS7 cause intellectual disability with speech delay, microcephaly, short stature, and aggressive behavior. Am J Hum Genet 2018;103:1045-52.
119. Darvish H, Azcona LJ, Alehabib E, Jamali F, Tafakhori A, et al. A novel PUS7 mutation causes intellectual disability with autistic and aggressive behaviors. Neurol Genet 2019;5:e356.
120. Aza-Blanc P, Cooper CL, Wagner K, Batalov S, Deveraux QL, et al. Identification of modulators of TRAIL-induced apoptosis via RNAi-based phenotypic screening. Mol Cell 2003;12:627-37.
121. McCleverty CJ, Hornsby M, Spraggon G, Kreusch A. Crystal structure of human Pus10, a novel pseudouridine synthase. J Mol Biol 2007;373:1243-54.
122. Nakayama T, Wu J, Galvin-Parton P, Weiss J, Andriola MR, et al. Deficient activity of alanyl-tRNA synthetase underlies an autosomal recessive syndrome of progressive microcephaly, hypomyelination, and epileptic encephalopathy. Hum Mutat 2017;38:1348-54.
123. Simons C, Griffin LB, Helman G, Golas G, Pizzino A, et al. Loss-of-function alanyl-tRNA synthetase mutations cause an autosomal-recessive early-onset epileptic encephalopathy with persistent myelination defect. Am J Hum Genet 2015;96:675-81.
124. Nafisinia M, Sobreira N, Riley L, Gold W, Uhlenberg B, et al. Mutations in RARS cause a hypomyelination disorder akin to Pelizaeus-Merzbacher disease. Eur J Hum Genet 2017;25:1134-41.
125. Wolf NI, Salomons GS, Rodenburg RJ, Pouwels PJ, Schieving JH, et al. Mutations in RARS cause hypomyelination. Ann Neurol 2014;76:134-9.
126. Taft RJ, Vanderver A, Leventer RJ, Damiani SA, Simons C, et al. Mutations in DARS cause hypomyelination with brain stem and spinal cord involvement and leg spasticity. Am J Hum Genet 2013;92:774-80.
127. Casey JP, McGettigan P, Lynam-Lennon N, McDermott M, Regan R, et al. Identification of a mutation in LARS as a novel cause of infantile hepatopathy. Mol Genet Metab 2012;106:351-8.
128. Casey JP, Slattery S, Cotter M, Monavari AA, Knerr I, et al. Clinical and genetic characterisation of infantile liver failure syndrome type 1, due to recessive mutations in LARS. J Inherit Metab Dis 2015;38:1085-92.
129. Lo WS, Gardiner E, Xu Z, Lau CF, Wang F, et al. Human tRNA synthetase catalytic nulls with diverse functions. Science 2014;345:328-32.
130. Hadchouel A, Wieland T, Griese M, Baruffini E, Lorenz-Depiereux B, et al. Biallelic mutations of methionyl-tRNA synthetase cause a specific type of pulmonary alveolar proteinosis prevalent on reunion island. Am J Hum Genet 2015;96:826-31.
131. Sun Y, Hu G, Luo J, Fang D, Yu Y, et al. Mutations in methionyl-tRNA synthetase gene in a Chinese family with interstitial lung and liver disease, postnatal growth failure and anemia. J Hum Genet 2017;62:647-51.
132. van Meel E, Wegner DJ, Cliften P, Willing MC, White FV, et al. Rare recessive loss-of-function methionyl-tRNA synthetase mutations presenting as a multi-organ phenotype. BMC Med Genet 2013;14:106.
133. Nowaczyk MJ, Huang L, Tarnopolsky M, Schwartzentruber J, Majewski J, et al. A novel multisystem disease associated with recessive mutations in the tyrosyl-tRNA synthetase (YARS) gene. Am J Med Genet A 2017;173:126-34.
134. Kopajtich R, Murayama K, Janecke AR, Haack TB, Breuer M, et al. Biallelic IARS mutations cause growth retardation with prenatal onset, intellectual disability, muscular hypotonia, and infantile hepatopathy. Am J Hum Genet 2016;99:414-22.
135. Nichols RC, Blinder J, Pai SI, Ge Q, Targoff IN, et al. Assignment of two human autoantigen genes-isoleucyl-tRNA synthetase locates to 9q21 and lysyl-tRNA synthetase locates to 16q23-q24. Genomics 1996;36:210-3.
136. Nichols RC, Raben N, Boerkoel CF, Plotz PH. Human isoleucyl-tRNA synthetase: sequence of the cDNA, alternative mRNA splicing, and the characteristics of an unusually long C-terminal extension. Gene 1995;155:299-304.
137. Orenstein N, Weiss K, Oprescu SN, Shapira R, Kidron D, et al. Bi-allelic IARS mutations in a child with intra-uterine growth retardation, neonatal cholestasis, and mild developmental delay. Clin Genet 2017;91:913-7.
138. Smigiel R, Biela M, Biernacka A, Stembalska A, Sasiadek M, et al. New evidence for association of recessive IARS gene mutations with hepatopathy, hypotonia, intellectual disability and growth retardation. Clin Genet 2017;92:671-3.
139. Vincent C, Tarbouriech N, Hartlein M. Genomic organization, cDNA sequence, bacterial expression, and purification of human seryl-tRNA synthase. Eur J Biochem 1997;250:77-84.
140. Friedman J, Smith DE, Issa MY, Stanley V, Wang R, et al. Biallelic mutations in valyl-tRNA synthetase gene VARS are associated with a progressive neurodevelopmental epileptic encephalopathy. Nat Commun 2019;10:707.
141. Hsieh SL, Campbell RD. Evidence that gene G7a in the human major histocompatibility complex encodes valyl-tRNA synthetase. Biochem J 1991;278:809-16.
142. Karaca E, Harel T, Pehlivan D, Jhangiani SN, Gambin T, et al. Genes that affect brain structure and function identified by rare variant analyses of mendelian neurologic disease. Neuron 2015;88:499-513.
143. Okur V, Ganapathi M, Wilson A, Chung WK. Biallelic variants in VARS in a family with two siblings with intellectual disability and microcephaly: case report and review of the literature. Cold Spring Harb Mol Case Stud 2018;4:a003301.
144. Siekierska A, Stamberger H, Deconinck T, Oprescu SN, Partoens M, et al. Biallelic VARS variants cause developmental encephalopathy with microcephaly that is recapitulated in vars knockout zebrafish. Nat Commun 2019;10:708.
145. Stephen J, Nampoothiri S, Banerjee A, Tolman NJ, Penninger JM, et al. Loss of function mutations in VARS encoding cytoplasmic valyl-tRNA synthetase cause microcephaly, seizures, and progressive cerebral atrophy. Hum Genet 2018;137:293-303.
146. Datta A, Ferguson A, Simonson C, Zannotto F, Michoulas A, et al. Case report. J Child Neurol 2017;32:403-7.
147. Kodera H, Osaka H, Iai M, Aida N, Yamashita A, et al. Mutations in the glutaminyl-tRNA synthetase gene cause early-onset epileptic encephalopathy. J Hum Genet 2015;60:97-101.
148. Leshinsky-Silver E, Ling J, Wu J, Vinkler C, Yosovich K, et al. Severe growth deficiency, microcephaly, intellectual disability, and characteristic facial features are due to a homozygous QARS mutation. Neurogenetics 2017;18:141-6.
149. Salvarinova R, Ye CX, Rossi A, Biancheri R, Roland EH, et al. Expansion of the QARS deficiency phenotype with report of a family with isolated supratentorial brain abnormalities. Neurogenetics 2015;16:145-9.
150. Vinkler C, Leshinsky-Silver E, Michelson M, Haas D, Lerman-Sagie T, et al. A newly recognized syndrome of severe growth deficiency, microcephaly, intellectual disability, and characteristic facial features. Eur J Med Genet 2014;57:288-92.
151. Zhang X, Ling J, Barcia G, Jing L, Wu J, et al. Mutations in QARS, encoding glutaminyl-tRNA synthetase, cause progressive microcephaly, cerebral-cerebellar atrophy, and intractable seizures. Am J Hum Genet 2014;94:547-58.
152. Basit S, Lee K, Habib R, Chen L, Umm-e-Kalsoom, et al. DFNB89, a novel autosomal recessive nonsyndromic hearing impairment locus on chromosome 16q21-q23.2. Hum Genet 2011;129:379-85.
153. Dickinson ME, Flenniken AM, Ji X, Teboul L, Wong MD, et al. High-throughput discovery of novel developmental phenotypes. Nature 2016;537:508-14.
154. Kohda M, Tokuzawa Y, Kishita Y, Nyuzuki H, Moriyama Y, et al. A comprehensive genomic analysis reveals the genetic landscape of mitochondrial respiratory chain complex deficiencies. PLoS Genet 2016;12:e1005679.
155. McLaughlin HM, Sakaguchi R, Liu C, Igarashi T, Pehlivan D, et al. Compound heterozygosity for loss-of-function lysyl-tRNA synthetase mutations in a patient with peripheral neuropathy. Am J Hum Genet 2010;87:560-6.
156. McMillan HJ, Humphreys P, Smith A, Schwartzentruber J, Chakraborty P, et al. Congenital Visual impairment and progressive microcephaly due to Lysyl-transfer ribonucleic acid (RNA) synthetase (KARS) mutations: the expanding phenotype of aminoacyl-transfer RNA synthetase mutations in human disease. J Child Neurol 2015;30:1037-43.
157. Murray CR, Abel SN, McClure MB, Foster J, Walke MI, et al. Novel causative variants in DYRK1A, KARS, and KAT6A associated with intellectual disability and additional phenotypic features. J Pediatr Genet 2017;6:77-83.
158. Santos-Cortez RL, Lee K, Azeem Z, Antonellis PJ, Pollock LM, et al. Mutations in KARS, encoding lysyl-tRNA synthetase, cause autosomal-recessive nonsyndromic hearing impairment DFNB89. Am J Hum Genet 2013;93:132-40.
159. Bonnefond L, Fender A, Rudinger-Thirion J, Giege R, Florentz C, et al. Toward the full set of human mitochondrial aminoacyl-tRNA synthetases: characterization of AspRS and TyrRS. Biochemistry 2005;44:4805-16.
160. Mizuguchi T, Nakashima M, Kato M, Yamada K, Okanishi T, et al. PARS2 and NARS2 mutations in infantile-onset neurodegenerative disorder. J Hum Genet 2017;62:525-9.
161. Seaver LH, DeRoos S, Andersen NJ, Betz B, Prokop J, et al. Lethal NARS2-related disorder associated with rapidly progressive intractable epilepsy and global brain atrophy. Pediatr Neurol 2018;89:26-30.
162. Simon M, Richard EM, Wang X, Shahzad M, Huang VH, et al. Mutations of human NARS2, encoding the mitochondrial asparaginyl-tRNA synthetase, cause nonsyndromic deafness and Leigh syndrome. PLoS Genet 2015;11:e1005097.
163. Sofou K, Kollberg G, Holmstrom M, Davila M, Darin N, et al. Whole exome sequencing reveals mutations in NARS2 and PARS2, encoding the mitochondrial asparaginyl-tRNA synthetase and prolyl-tRNA synthetase, in patients with Alpers syndrome. Mol Genet Genomic Med 2015;3:59-68.
164. Vanlander AV, Menten B, Smet J, De Meirleir L, Sante T, et al. Two siblings with homozygous pathogenic splice-site variant in mitochondrial asparaginyl-tRNA synthetase (NARS2). Hum Mutat 2015;36:222-31.
165. Ciara E, Rokicki D, Lazniewski M, Mierzewska H, Jurkiewicz E, et al. Clinical and molecular characteristics of newly reported mitochondrial disease entity caused by biallelic PARS2 mutations. J Hum Genet 2018;63:473-85.
166. Edvardson S, Shaag A, Kolesnikova O, Gomori JM, Tarassov I, et al. Deleterious mutation in the mitochondrial arginyl-transfer RNA synthetase gene is associated with pontocerebellar hypoplasia. Am J Hum Genet 2007;81:857-62.
167. Pronicka E, Piekutowska-Abramczuk D, Ciara E, Trubicka J, Rokicki D, et al. New perspective in diagnostics of mitochondrial disorders: two years’ experience with whole-exome sequencing at a national paediatric centre. J Transl Med 2016;14:174.
168. Yin X, Tang B, Mao X, Peng J, Zeng S, et al. The genotypic and phenotypic spectrum of PARS2-related infantile-onset encephalopathy. J Hum Genet 2018;63:971-80.
169. Alkhateeb AM, Aburahma SK, Habbab W, Thompson IR. Novel mutations in WWOX, RARS2, and C10orf2 genes in consanguineous Arab families with intellectual disability. Metab Brain Dis 2016;31:901-7.
170. Cassandrini D, Cilio MR, Bianchi M, Doimo M, Balestri M, et al. Pontocerebellar hypoplasia type 6 caused by mutations in RARS2: definition of the clinical spectrum and molecular findings in five patients. J Inherit Metab Dis 2013;36:43-53.
171. Li Z, Schonberg R, Guidugli L, Johnson AK, Arnovitz S, et al. A novel mutation in the promoter of RARS2 causes pontocerebellar hypoplasia in two siblings. J Hum Genet 2015;60:363-9.
172. Rankin J, Brown R, Dobyns WB, Harington J, Patel J, et al. Pontocerebellar hypoplasia type 6: a British case with PEHO-like features. Am J Med Genet A 2010;152A:2079-84.
173. Tzagoloff A, Shtanko A. Mitochondrial and cytoplasmic isoleucyl-, glutamyl- and arginyl-tRNA synthetases of yeast are encoded by separate genes. Eur J Biochem 1995;230:582-6.
174. Martinez-Dominguez MT, Justesen J, Kruse TA, Hansen LL. Assignment of the human mitochondrial tryptophanyl-tRNA synthetase (WARS2) to 1p13.3-->p13.1 by radiation hybrid mapping. Cytogenet Cell Genet 1998;83:249-50.
175. Theisen BE, Rumyantseva A, Cohen JS, Alcaraz WA, Shinde DN, et al. Deficiency of WARS2, encoding mitochondrial tryptophanyl tRNA synthetase, causes severe infantile onset leukoencephalopathy. Am J Med Genet A 2017;173:2505-10.
176. Wortmann SB, Timal S, Venselaar H, Wintjes LT, Kopajtich R, et al. Biallelic variants in WARS2 encoding mitochondrial tryptophanyl-tRNA synthase in six individuals with mitochondrial encephalopathy. Hum Mutat 2017;38:1786-95.
177. Boccaletto P, Machnicka MA, Purta E, Piątkowski P, Bagiński B, et al. MODOMICS: a database of RNA modification pathways. 2017 update. Nucleic Acids Res 2018;46:D303-7.
178. Ogura T, Tomoyasu T, Yuki T, Morimura S, Begg KJ, et al. Structure and function of the ftsH gene in Escherichia coli. Res Microbiol 1991;142:279-82.
179. Bugl H, Fauman EB, Staker BL, Zheng F, Kushner SR, et al. RNA methylation under heat shock control. Mol Cell 2000;6:349-60.
180. Guy MP, Shaw M, Weiner CL, Hobson L, Stark Z, et al. Defects in tRNA anticodon loop 2’-O-Methylation are implicated in nonsyndromic X-linked intellectual disability due to mutations in FTSJ1. Hum Mutat 2015;36:1176-87.
181. Marchand V, Pichot F, Thuring K, Ayadi L, Freund I, et al. Next-generation sequencing-based ribomethseq protocol for analysis of tRNA 2’-O-Methylation. Biomolecules 2017;7:13.
182. Panebianco F, Kelly LM, Liu P, Zhong S, Dacic S, et al. THADA fusion is a mechanism of IGF2BP3 activation and IGF1R signaling in thyroid cancer. Proc Natl Acad Sci U S A 2017;114:2307-12.
183. Takano K, Nakagawa E, Inoue K, Kamada F, Kure S, et al. A loss-of-function mutation in the FTSJ1 gene causes nonsyndromic X-linked mental retardation in a Japanese family. Am J Med Genet B Neuropsychiatr Genet 2008;147B:479-84.
184. Honda S, Hayashi S, Imoto I, Toyama J, Okazawa H, et al. Copy-number variations on the X chromosome in Japanese patients with mental retardation detected by array-based comparative genomic hybridization analysis. J Hum Genet 2010;55:590-9.
185. Bonnet C, Gregoire MJ, Brochet K, Raffo E, Leheup B, et al. Pure de-novo 5 Mb duplication at Xp11.22-p11.23 in a male. J Hum Genet 2006;51:815.
186. El-Hattab AW, Bournat J, Eng PA, Wu JBS, Walker BA, et al. Microduplication of Xp11.23p11.3 with effects on cognition, behavior, and craniofacial development. Clin Genet 2011;79:531-8.
187. Froyen G, Bauters M, Boyle J, van Esch H, Govaerts K, et al. Loss of SLC38A5 and FTSJ1 at Xp11.23 in three brothers with non-syndromic mental retardation due to a microdeletion in an unstable genomic region. Hum Genet 2007;121:539-47.
188. Torres AG, Pineyro D, Rodriguez-Escriba M, Camacho N, Reina O, et al. Inosine modifications in human tRNAs are incorporated at the precursor tRNA level. Nucleic Acids Res 2015;43:5145-57.
189. Songe-Moller L, van den Born E, Leihne V, Vagbo CB, Kristoffersen T, et al. Mammalian ALKBH8 possesses tRNA methyltransferase activity required for the biogenesis of multiple wobble uridine modifications implicated in translational decoding. Mol Cell Biol 2010;30:1814-27.
190. van den Born E, Vagbo CB, Songe-Moller L, Leihne V, Lien GF, et al. ALKBH8-mediated formation of a novel diastereomeric pair of wobble nucleosides in mammalian tRNA. Nat Commun 2011;2:172.
191. Philipp M, John F, Ringli C. The cytosolic thiouridylase CTU2 of Arabidopsis thaliana is essential for posttranscriptional thiolation of tRNAs and influences root development. BMC Plant Biol 2014;14:109.
192. Downey M, Houlsworth R, Maringele L, Rollie A, Brehme M, et al. A genome-wide screen identifies the evolutionarily conserved KEOPS complex as a telomere regulator. Cell 2006;124:1155-68.
193. Srinivasan M, Mehta P, Yu Y, Prugar E, Koonin EV, et al. The highly conserved KEOPS/EKC complex is essential for a universal tRNA modification, t6A. EMBO J 2011;30:873-81.
194. Huang B, Johansson MJ, Bystrom AS. An early step in wobble uridine tRNA modification requires the Elongator complex. RNA 2005;11:424-36.
195. Esberg A, Huang B, Johansson MJ, Bystrom AS. Elevated levels of two tRNA species bypass the requirement for elongator complex in transcription and exocytosis. Mol Cell 2006;24:139-48.
196. Simos G, Tekotte H, Grosjean H, Segref A, Sharma K, et al. Nuclear pore proteins are involved in the biogenesis of functional tRNA. EMBO J 1996;15:2270-84.
197. Lecointe F, Simos G, Sauer A, Hurt EC, Motorin Y, et al. Characterization of yeast protein Deg1 as pseudouridine synthase (Pus3) catalyzing the formation of psi 38 and psi 39 in tRNA anticodon loop. J Biol Chem 1998;273:1316-23.
198. Paiva ARB, Lynch DS, Melo US, Lucato LT, Freua F, et al. PUS3 mutations are associated with intellectual disability, leukoencephalopathy, and nephropathy. Neurol Genet 2019;5:e306.
199. Fang H, Zhang L, Xiao B, Long H, Yang L. Compound heterozygous mutations in PUS3 gene identified in a Chinese infant with severe epileptic encephalopathy and multiple malformations. Neurol Sci 2020;41:465-7.
200. Behm-Ansmant I, Urban A, Ma X, Yu YT, Motorin Y, et al. The Saccharomyces cerevisiae U2 snRNA:pseudouridine-synthase Pus7p is a novel multisite-multisubstrate RNA:Psi-synthase also acting on tRNAs. RNA 2003;9:1371-82.
201. Ma X, Zhao X, Yu YT. Pseudouridylation (Psi) of U2 snRNA in S. cerevisiae is catalyzed by an RNA-independent mechanism. EMBO J 2003;22:1889-97.
202. Decatur WA, Schnare MN. Different mechanisms for pseudouridine formation in yeast 5S and 5.8S rRNAs. Mol Cell Biol 2008;28:3089-100.
203. Schwartz S, Bernstein DA, Mumbach MR, Jovanovic M, Herbst RH, et al. Transcriptome-wide mapping reveals widespread dynamic-regulated pseudouridylation of ncRNA and mRNA. Cell 2014;159:148-62.
204. Wu G, Xiao M, Yang C, Yu YT. U2 snRNA is inducibly pseudouridylated at novel sites by Pus7p and snR81 RNP. EMBO J 2011;30:79-89.
205. Guzzi N, Ciesla M, Ngoc PCT, Lang S, Arora S, et al. Pseudouridylation of tRNA-derived fragments steers translational control in stem cells. Cell 2018;173:1204-16.e26.
206. Brennan T, Sundaralingam M. Structure of transfer RNA molecules containing the long variable loop. Nucleic Acids Res 1976;3:3235-50.
207. Sun FJ, Caetano-Anollés G. The evolutionary significance of the long variable arm in transfer RNA. Complexity 2009;14:26-39.
208. Komara M, Al-Shamsi AM, Ben-Salem S, Ali BR, Al-Gazali L. A novel single-nucleotide deletion (c.1020delA) in NSUN2 causes intellectual disability in an emirati child. J Mol Neurosci 2015;57:393-9.
209. Steinberg S, Cedergren R. A correlation between N2-dimethylguanosine presence and alternate tRNA conformers. RNA 1995;1:886-91.
210. Vakiloroayaei A, Shah NS, Oeffinger M, Bayfield MA. The RNA chaperone La promotes pre-tRNA maturation via indiscriminate binding of both native and misfolded targets. Nucleic Acids Res 2017;45:11341-55.
211. Chou HJ, Donnard E, Gustafsson HT, Garber M, Rando OJ. Transcriptome-wide analysis of roles for tRNA modifications in translational regulation. Mol Cell 2017;68:978-92.e4.
212. Gustavsson M, Ronne H. Evidence that tRNA modifying enzymes are important in vivo targets for 5-fluorouracil in yeast. RNA 2008;14:666-74.
213. Torabi N, Kruglyak L. Variants in SUP45 and TRM10 underlie natural variation in translation termination efficiency in Saccharomyces cerevisiae. PLoS Genet 2011;7:e1002211.
214. Helm M, Brule H, Degoul F, Cepanec C, Leroux JP, et al. The presence of modified nucleotides is required for cloverleaf folding of a human mitochondrial tRNA. Nucleic Acids Res 1998;26:1636-43.
215. Chen CP, Chern SR, Wu PS, Chen SW, Lai ST, et al. Prenatal diagnosis of a 3.2-Mb 2p16.1-p15 duplication associated with familial intellectual disability. Taiwan J Obstet Gynecol 2018;57:578-82.
216. Piccione M, Piro E, Serraino F, Cavani S, Ciccone R, et al. Interstitial deletion of chromosome 2p15-16.1: report of two patients and critical review of current genotype-phenotype correlation. Eur J Med Genet 2012;55:238-44.
217. Lovrecic L, Gnan C, Baldan F, Franzoni A, Bertok S, et al. Microduplication in the 2p16.1p15 chromosomal region linked to developmental delay and intellectual disability. Mol Cytogenet 2018;11:39.
218. Peter B, Matsushita M, Oda K, Raskind W. De novo microdeletion of BCL11A is associated with severe speech sound disorder. Am J Med Genet A 2014;164A:2091-6.
219. Balci TB, Sawyer SL, Davila J, Humphreys P, Dyment DA. Brain malformations in a patient with deletion 2p16.1: a refinement of the phenotype to BCL11A. Eur J Med Genet 2015;58:351-4.
220. Schimmel P. The emerging complexity of the tRNA world: mammalian tRNAs beyond protein synthesis. Nat Rev Mol Cell Biol 2018;19:45-58.
221. Waltl S. Progressive microcephaly is caused by compound-heterozygous mutations in QARS. Clin Genet 2014;86:508-9.
222. Scheper GC, van der Klok T, van Andel RJ, van Berkel CG, Sissler M, et al. Mitochondrial aspartyl-tRNA synthetase deficiency causes leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation. Nat Genet 2007;39:534-9.
223. Moulinier L, Ripp R, Castillo G, Poch O, Sissler M. MiSynPat: an integrated knowledge base linking clinical, genetic, and structural data for disease-causing mutations in human mitochondrial aminoacyl-tRNA synthetases. Hum Mutat 2017;38:1316-24.
224. Puffenberger EG, Jinks RN, Sougnez C, Cibulskis K, Willert RA, et al. Genetic mapping and exome sequencing identify variants associated with five novel diseases. PLoS One 2012;7:e28936.
